The role of genetic factors in multiple sclerosis susceptibility

Ebers, George C.; Sadovnick, A. Dessa

doi:10.1016/0165-5728(94)90225-9

Cited by 170 publications

(67 citation statements)

References 120 publications

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“…In addition to a genetic predisposition (Ebers and Sadovnick 1994), epidemiological studies suggest a strong association between increased MS prevalence and particular diets (Antonovsky et al 1965;Cendrowski et al 1969;Berr et al 1989;Tola et al 1994). Studies conducted on dietary factors associated with MS have included fat consumption, particularly saturated animal fat (Payne 2001); breastfeeding duration (Isaacs et al 2010); and the intake of sweets (Antonovsky et al 1965), alcohol (Berr et al 1989;Sepcic et al 1993), smoked meat products (Sepcic et al 1993), coffee, and tea (Tola et al 1994).…”

Section: Demyelination/remyelination and Nutrientsmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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Demyelination is a pathological process characterized by the loss of myelin around axons. In the central nervous system, oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Remyelination is a regenerative process by which myelin sheaths are restored to demyelinated axons, resolving functional deficits. This process is often deficient in demyelinating diseases such as multiple sclerosis (MS), and the reasons for the failure of repair mechanisms remain unclear. The characterization of these mechanisms and the factors involved in the proliferation, recruitment, and differentiation of oligodendroglial progenitor cells is key in designing strategies to improve remyelination in demyelinating disorders. First, a very dynamic combination of different molecules such as growth factors, cytokines, chemokines, and different signaling pathways is tightly regulated during the remyelination process. Second, factors unrelated to this pathology, i.e., age and genetic background, may impact disease progression either positively or negatively, and in particular, age-related remyelination failure has been proven to involve oligodendroglial cells aging and their intrinsic capacities among other factors. Third, nutrients may either help or hinder disease progression. Experimental evidence supports the anti-inflammatory role of omega-6 and omega-3 polyunsaturated fatty acids through the competitive inhibition of arachidonic acid, whose metabolites participate in inflammation, and the reduction in T cell proliferation. In turn, vitamin D intake and synthesis have been associated with lower MS incidence levels, while vitamin D-gene interactions might be involved in the pathogenesis of MS. Finally, dietary polyphenols have been reported to mitigate demyelination by modulating the immune response.

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Section: Demyelination/remyelination and Nutrientsmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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“…The importance of the genetic component is illustrated by the fact that the risk of MS in siblings to MS patients is 20-to 40-fold higher than the risk in the general population. 3 Four previous whole-genome linkage screens have suggested the existence of several chromosomal regions containing MS susceptibility genes, yet none of these regions, apart from the HLA region on chromosome 6p21, appears to harbor a major MS susceptibility locus (reviewed in Oksenberg et al 4 ). At the same time, in a recently published meta-analysis that combined raw genotyping data from all published whole-genome linkage screens in MS, it was shown that there exist overlapping regions, which may contain genes predisposing to MS; 5 in addition to the HLA region, regions on chromosome 17q21 and chromosome 22q13 showed suggestive linkage.…”

Section: Introductionmentioning

confidence: 99%

Two genes encoding immune-regulatory molecules (LAG3 and IL7R) confer susceptibility to multiple sclerosis

et al. 2005

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Multiple sclerosis (MS) is a T-cell-mediated disease of the central nervous system, characterized by damage to myelin and axons, resulting in progressive neurological disability. Genes may influence susceptibility to MS, but results of association studies are inconsistent, aside from the identification of HLA class II haplotypes. Whole-genome linkage screens in MS have both confirmed the importance of the HLA region and uncovered non-HLA loci that may harbor susceptibility genes. In this twostage analysis, we determined genotypes, in up to 672 MS patients and 672 controls, for 123 single-nucleotide polymorphisms (SNPs) in 66 genes. Genes were chosen based on their chromosomal positions or biological functions. In stage one, 22 genes contained at least one SNP for which the carriage rate for one allele differed significantly (Po0.08) between patients and controls. After additional genotyping in stage two, two genes-each containing at least three significantly (Po0.05) associated SNPs-conferred susceptibility to MS: LAG3 on chromosome 12p13, and IL7R on 5p13. LAG3 inhibits activated T cells, while IL7R is necessary for the maturation of T and B cells. These results imply that germline allelic variation in genes involved in immune homeostasis-and, by extension, derangement of immune homeostasis-influence the risk of MS.

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“…An increased family incidence and association with certain HLA allotypes suggests genetic susceptibility (Ebers & Sadovnick, 1994). The genetic epidemiology indicates that MS is not a single-gene disorder (Ebers, 1994;Compston, 1997;Noseworthy, 1999).…”

Section: Etiological Factors Of Msmentioning

confidence: 99%

Multiple sclerosis and vitamin D: an update

et al. 2004

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MS is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS), with an etiology that is not yet fully understood. The prevalence of MS is highest where environmental supplies of vitamin D are lowest. It is well recognized that the active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH) 2 D), is a natural immunoregulator with anti-inflammatory action. The mechanism by which vitamin D nutrition is thought to influence MS involves paracrine or autocrine metabolism of 25OHD by cells expressing the enzyme 1a-OHase in peripheral tissues involved in immune and neural function. Administration of the active metabolite 1,25-(OH) 2 D in mice and rats with experimental allergic encephalomyelitis (EAE, an animal model of MS) not only prevented, but also reduced disease activity. 1,25-(OH) 2 D alters dendritic cell and T-cell function and regulates macrophages in EAE. Interestingly, 1,25-(OH) 2 D is thought to be operating on CNS constituent cells as well. Vitamin D deficiency is caused by insufficient sunlight exposure or low dietary vitamin D 3 intake. Subtle defects in vitamin D metabolism, including genetic polymorphisms related to vitamin D, might possibly be involved as well. Optimal 25OHD serum concentrations, throughout the year, may be beneficial for patients with MS, both to obtain immune-mediated suppression of disease activity, and also to decrease disease-related complications, including increased bone resorption, fractures, and muscle weakness.

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The role of genetic factors in multiple sclerosis susceptibility

Cited by 170 publications

References 120 publications

Nutritional factors and aging in demyelinating diseases

Nutritional factors and aging in demyelinating diseases

Two genes encoding immune-regulatory molecules (LAG3 and IL7R) confer susceptibility to multiple sclerosis

Multiple sclerosis and vitamin D: an update

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